ArticleNature immunology2023
CTLA-4 tail fusion enhances CAR-T antitumor immunity.
Article in Nature immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Strategies and mechanisms for the enhancement of chimeric antigen receptor T-cell functions.Science China. Life sciences · 2026Pooled it
- Engineered CTLA-4 targeting chimeras for targeted protein degradation and immune synapse reprogramming.bioRxiv : the preprint server for biology · 2026Article
- Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.Signal transduction and targeted therapy · 2026Review
- Macrophage Trogocytosis of Tumor Cells Drives the Immunosuppression of Tumor Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Immunotherapy in acute myeloid leukemia: The antibodies, TriKEs, and CARs on the arduous road to cure.Blood reviews · 2026Review
- Trogocytosis in cancer immunity and cellular immunotherapy: mechanisms, therapeutic challenges, and translational opportunities.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Special Issue "State-of-the-Art Cancer Immunotherapies-2nd Edition".International journal of molecular sciences · 2026Article
- IL-5 CAR-T cell therapy induces effective remission in hypereosinophilic disorders.Journal of hematology & oncology · 2026Article
- PD-1 suppresses CAR signaling by forming the inhibitory signalosome colocalizing to CAR microclusters.Communications biology · 2026Article
- CAR-T cell signaling dynamics, rational design principles and artificial intelligence for next-generation chimeric antigen receptors.Frontiers in immunology · 2026Review
- Challenges in the Vaccination of HIV-Infected Individuals.Vaccines · 2025Review
- In vivo CAR-T cell engineering: concept, research progress, potential challenges and enhancement strategies.Experimental hematology & oncology · 2025Review
- Current status of chimeric antigen receptor T cell therapy and its exhaustion mechanism.Immunotherapy · 2025Review
- CAR-T cell therapy for glioblastoma: advances, challenges, and future directions.Annals of medicine and surgery (2012) · 2025Review
- Molecular Dynamics of Trogocytosis and Other Contact-Dependent Cell Trafficking Mechanisms in Tumor Pathogenesis.Cancers · 2025Review
- Commentary: is trogocytosis relevant for chimeric antigen receptor-T cells?The oncologist · 2025Article
- The Role of Abatacept on Inflammation and Fibrosis in Hypochlorous Acid-Induced Fibrosis Mice.International journal of rheumatic diseases · 2025Article
- Tailoring CAR surface density and dynamics to improve CAR-T cell therapy.Journal for immunotherapy of cancer · 2025Review
- Review
- Dissecting the role of CAR signaling architectures on T cell activation and persistence using pooled screens and single-cell sequencing.Science advances · 2025Article
Corrections and comments
- Update of
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Chimeric antigen receptor (CAR)-T cells are powerful therapeutics; however, their efficacy is often hindered by critical hurdles. Here utilizing the endocytic feature of the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) cytoplasmic tail, we reprogram CAR function and substantially enhance CAR-T efficacy in vivo. CAR-T cells with monomeric, duplex or triplex CTLA-4 cytoplasmic tails (CCTs) fused to the C terminus of CAR exhibit a progressive increase in cytotoxicity under repeated stimulation, accompanied by reduced activation and production of proinflammatory cytokines. Further characterization reveals that CARs with increasing CCT fusion show a progressively lower surface expression, regulated by their constant endocytosis, recycling and degradation under steady state. The molecular dynamics of reengineered CAR with CCT fusion results in reduced CAR-mediated trogocytosis, loss of tumor antigen and improved CAR-T survival. CARs with either monomeric (CAR-1CCT) or duplex CCTs (CAR-2CCT) have superior antitumor efficacy in a relapsed leukemia model. Single-cell RNA sequencing and flow cytometry analysis reveal that CAR-2CCT cells retain a stronger central memory phenotype and exhibit increased persistence. These findings illuminate a unique strategy for engineering therapeutic T cells and improving CAR-T function through synthetic CCT fusion, which is orthogonal to other cell engineering techniques.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.